Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic dystrophy

Abstract

Background: Excessive daytime sleepiness is a common symptom of myotonic dystrophy. Psychostimulants are drugs that are increasingly used to treat hypersomnia in myotonic dystrophy.

Objectives: To assess the effects of psychostimulants in myotonic dystrophy patients with hypersomnia.

Search methods: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP on 5 January 2023. We also checked the bibliographies of identified papers and made enquiries of the authors of the papers.

Selection criteria: We considered all randomised controlled trials that have evaluated any type of psychostimulant (versus a placebo or no treatment) in children or adults with myotonic dystrophy, confirmed by clinical and electromyographic diagnostic, or genetic testing, and hypersomnia.

Data collection and analysis: Two review authors independently scrutinised potentially relevant papers for study inclusion, with any disagreements resolved by discussion. Two review authors independently performed data extraction. We obtained unpublished data from some study authors. We assessed the methodological quality of trials and applied GRADE to assess the certainty of evidence. Review authors did not contribute to eligibility or risk of bias assessment or data extraction of trials in which they had participated. When cross-over trials were included in the analysis, treatment effects were summarised as mean difference (MD) between treatment effects and standard error, and analysed by generic inverse variance.

Main results: We included six trials (136 participants). All studies included only adult outpatients, aged from 18 to 70 years old, and followed them only in the short term (up to four weeks). Five trials had a cross-over design. We judged five trials as being at low risk of bias. Primary outcome Data for mean improvement in the Maintenance of Wakefulness Test were available from three trials. The MD was 3.59 (95% confidence interval (CI) -0.06 to 7.24) minutes, and there was marked heterogeneity across studies (I² = 71%). We downgraded the certainty of evidence to very low for inconsistency and imprecision. Secondary outcomes Data for mean improvement in the Epworth Sleepiness Scale were available from five trials. The MD was -2.55 (95% CI -4.00 to -1.11, P < 0.001) in favour of modafinil with considerable heterogeneity across studies (I² = 80%). We downgraded the certainty of evidence to low for inconsistency. The effects of psychostimulants on excessive daytime sleepiness as assessed by the Multiple Sleep Latency Test (MD -1.82, 95% CI -5.57 to 1.93; P = 0.34; very low certainty evidence) and on quality of life (MD 1.27, 95% CI -3.63 to 6.17; I² = 0%; very low certainty evidence) were very uncertain. The risk ratio for experiencing adverse events was 1.70 (95% CI 0.75 to 3.85; P = 0.20; I² = 0%; low certainty evidence). No trial evaluated our primary or secondary outcomes in the long term. We were not able to perform planned subgroup analyses as none of the trials provided relevant data.

Authors' conclusions: In myotonic dystrophy, the effects of psychostimulants on excessive daytime sleepiness as assessed by the Maintenance of Wakefulness Test or Multiple Sleep Latency Test and on quality of life are very uncertain. Psychostimulants may improve hypersomnia as self-evaluated by the Epworth Sleepiness Scale and may increase the risk of adverse events. More randomised trials are needed to evaluate the efficacy and safety of psychostimulants in both the short and long term.

Trial registration: ClinicalTrials.gov NCT01421992.